DOTA-TATE
{{Short description|Eight amino-acid long peptide covalently bonded to a DOTA chelator}}
{{Use dmy dates|date=December 2019}}
{{chembox
|ImageFile = DOTATATE.svg
|OtherNames = DOTA-(Tyr3)-octreotate
|Section1 = {{Chembox Identifiers
|CASNo = 177943-89-4
|CASNo_Ref = {{cascite|correct|CAS}}
|UNII_Ref = {{fdacite|correct|FDA}}
|UNII = 99R86Y6V0M
|PubChem = 11170867
|ChemSpiderID = 9345959
|SMILES = C[C@H]([C@H]1C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N1)CCCCN)CC2=CNC3=CC=CC=C32)CC4=CC=C(C=C4)O)NC(=O)[C@@H](CC5=CC=CC=C5)NC(=O)CN6CCN(CCN(CCN(CC6)CC(=O)O)CC(=O)O)CC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)O)O
|InChI = 1/C65H90N14O19S2/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98)/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+/m1/s1
|InChIKey = QVFLVLMYXXNJDT-CSBVGUNJBN
|StdInChI = 1S/C65H90N14O19S2/c1-38(80)56-64(96)73-51(63(95)75-57(39(2)81)65(97)98)37-100-99-36-50(72-59(91)47(28-40-10-4-3-5-11-40)68-52(83)32-76-20-22-77(33-53(84)85)24-26-79(35-55(88)89)27-25-78(23-21-76)34-54(86)87)62(94)70-48(29-41-15-17-43(82)18-16-41)60(92)71-49(30-42-31-67-45-13-7-6-12-44(42)45)61(93)69-46(58(90)74-56)14-8-9-19-66/h3-7,10-13,15-18,31,38-39,46-51,56-57,67,80-82H,8-9,14,19-30,32-37,66H2,1-2H3,(H,68,83)(H,69,93)(H,70,94)(H,71,92)(H,72,91)(H,73,96)(H,74,90)(H,75,95)(H,84,85)(H,86,87)(H,88,89)(H,97,98)/t38-,39-,46+,47-,48+,49-,50+,51+,56+,57+/m1/s1
|StdInChIKey = QVFLVLMYXXNJDT-CSBVGUNJSA-N
}}
|Section2 = {{Chembox Properties
|C=65 | H=90 | N=14 | O=19 | S=2
}}
}}
DOTA-TATE (DOTATATE,{{cite journal | vauthors = Nockel P, Millo C, Keutgen X, Klubo-Gwiezdzinska J, Shell J, Patel D, Nilubol N, Herscovitch P, Sadowski SM, Kebebew E | title = The Rate and Clinical Significance of Incidental Thyroid Uptake as Detected by Gallium-68 DOTATATE Positron Emission Tomography/Computed Tomography | journal = Thyroid | volume = 26 | issue = 6 | pages = 831–5 | date = June 2016 | pmid = 27094616 | pmc = 4913484 | doi = 10.1089/thy.2016.0174}} DOTA-octreotate, oxodotreotide, DOTA-(Tyr3)-octreotate,{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/5326939|title=[Tyr3]octreotate|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|access-date=2018-04-02}} and DOTA-0-Tyr3-Octreotate) is an eight amino acid long peptide, with a covalently bonded DOTA bifunctional chelator.
DOTA-TATE can be reacted with the radionuclides gallium-68 (T1/2 = 68 min), lutetium-177 (T1/2 = 6.65 d) and copper-64 (T1/2 = 12.7 h) to form radiopharmaceuticals for positron emission tomography (PET) imaging or radionuclide therapy. 177Lu DOTA-TATE therapy is a form of peptide receptor radionuclide therapy (PRRT) which targets somatostatin receptors (SSR).{{cite book|last1=Papotti|first1=M.|last2=Herder|first2=W. W. de|title=Neuroendocrine Tumors: A Multidisciplinary Approach|date=2015|publisher=Karger Medical and Scientific Publishers|isbn=9783318027730|page=77|url=https://books.google.com/books?id=pHC9CgAAQBAJ&pg=PT87}}{{cite book|last1=Aktolun|first1=Cumali|last2=Goldsmith|first2=Stanley J.|title=Nuclear Medicine Therapy: Principles and Clinical Applications|date=2012|publisher=Springer|isbn=9781461440215|page=364|url=https://books.google.com/books?id=j-FgjR2qtfgC&pg=PA364}} In that form of application it is a form of targeted drug delivery.
Chemistry and mechanism of action
DOTA-TATE is a compound containing tyrosine3-octreotate, an SSR agonist, and the bifunctional chelator DOTA (tetraxetan).{{Cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/121841|title=Tetraxetan|last=Pubchem|website=pubchem.ncbi.nlm.nih.gov|access-date=2018-04-02}}{{cite journal | vauthors = Fani M, Nicolas GP, Wild D | title = Somatostatin Receptor Antagonists for Imaging and Therapy | journal = Journal of Nuclear Medicine | volume = 58 | issue = Suppl 2 | pages = 61S–66S | date = September 2017 | pmid = 28864614 | doi = 10.2967/jnumed.116.186783 | doi-access = free}} SSRs are found with high density in numerous malignancies, including CNS, breast, lung, and lymphatics.{{cite journal | vauthors = Reubi JC, Laissue JA | title = Multiple actions of somatostatin in neoplastic disease | journal = Trends in Pharmacological Sciences | volume = 16 | issue = 3 | pages = 110–5 | date = March 1995 | pmid = 7792931 | doi = 10.1016/S0165-6147(00)88992-0 }} The role of SSR agonists (i.e. somatostatin and its analogs such as octreotide, somatuline and vapreotide) in neuroendocrine tumours (NETs) is well established,{{cite journal | vauthors = Mazziotti G, Mosca A, Frara S, Vitale G, Giustina A | title = Somatostatin analogs in the treatment of neuroendocrine tumors: current and emerging aspects | journal = Expert Opinion on Pharmacotherapy | volume = 18 | issue = 16 | pages = 1679–1689 | date = November 2017 | pmid = 29067877 | doi = 10.1080/14656566.2017.1391217 | s2cid = 46747267 }} and massive SSR overexpression is present in several NETs. (Tyr3)-octreotate binds the transmembrane receptors of NETs with highest activity for SSR2 and is actively transported into the cell via endocytosis, allowing trapping of the radioactivity and increasing the probability of the desired double-strand DNA breakage (for tumour control). Trapping improves the probability of this kind of effect due to the relatively short range of the beta particles emitted by 177Lu, which have a maximum range in tissue of <2 mm.{{cite journal | vauthors = Emmett L, Willowson K, Violet J, Shin J, Blanksby A, Lee J | title = 177 PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy | journal = Journal of Medical Radiation Sciences | volume = 64 | issue = 1 | pages = 52–60 | date = March 2017 | pmid = 28303694 | pmc = 5355374 | doi = 10.1002/jmrs.227}}{{cite journal | vauthors = Reubi JC, Schonbrunn A | title = Illuminating somatostatin analog action at neuroendocrine tumor receptors | journal = Trends in Pharmacological Sciences | volume = 34 | issue = 12 | pages = 676–88 | date = December 2013 | pmid = 24183675 | pmc = 3883302 | doi = 10.1016/j.tips.2013.10.001}} Bystander effects include cellular damage by free radical formation.
Clinical applications
=Gallium-68 DOTA-TATE=
{{More|Gallium scan#Gallium DOTA scans}}
68Ga DOTA-TATE (gallium-68 dotatate, GaTate) is used to measure tumor SSR density and whole-body bio-distribution via PET imaging.{{cite journal | vauthors = Hofman MS, Kong G, Neels OC, Eu P, Hong E, Hicks RJ | title = High management impact of Ga-68 DOTATATE (GaTate) PET/CT for imaging neuroendocrine and other somatostatin expressing tumours | journal = Journal of Medical Imaging and Radiation Oncology | volume = 56 | issue = 1 | pages = 40–7 | date = February 2012 | pmid = 22339744 | doi = 10.1111/j.1754-9485.2011.02327.x| s2cid = 21843609 | doi-access = free }}{{cite journal | vauthors = Breeman WA, de Blois E, Sze Chan H, Konijnenberg M, Kwekkeboom DJ, Krenning EP | title = (68)Ga-labeled DOTA-peptides and (68)Ga-labeled radiopharmaceuticals for positron emission tomography: current status of research, clinical applications, and future perspectives | journal = Seminars in Nuclear Medicine | volume = 41 | issue = 4 | pages = 314–321 | date = July 2011 | pmid = 21624565 | doi = 10.1053/j.semnuclmed.2011.02.001 }} 68Ga DOTA-TATE imagery has a much higher sensitivity and resolution compared to 111In octreotide gamma camera or SPECT scans, due to intrinsic modality differences. It is commonly used to confirm the presence of paragangliomas and pheochromocytomas.{{Cite journal |last1=Chang |first1=Chian A. |last2=Pattison |first2=David A. |last3=Tothill |first3=Richard W. |last4=Kong |first4=Grace |last5=Akhurst |first5=Tim J. |last6=Hicks |first6=Rodney J. |last7=Hofman |first7=Michael S. |date=2016-08-17 |title=68Ga-DOTATATE and 18F-FDG PET/CT in Paraganglioma and Pheochromocytoma: utility, patterns and heterogeneity |journal=Cancer Imaging |volume=16 |issue=1 |pages=22 |doi=10.1186/s40644-016-0084-2 |issn=1740-5025 |pmc=4989291 |pmid=27535829 |doi-access=free }}
= Copper-64 DOTA-TATE =
Copper (64Cu) oxodotreotide or copper Cu 64 dotatate, sold under the brand name Detectnet, is a radioactive diagnostic agent indicated for use with positron emission tomography (PET) for localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults. It was FDA approved in September 2020. These are the same indications for as the gallium DOTA-TATE scans, but Cu-64 has advantages over Ga-68 in having a 12-hour half life rather than the much shorter one-hour half life of Ga-68, making it easier to transport from central production locations. {{cite web | url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213227Orig1s000ltr.pdf | archive-url=https://web.archive.org/web/20201020222429/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2020/213227Orig1s000ltr.pdf | url-status=dead | archive-date=20 October 2020 | title=FDA approval letter | date=3 September 2020 | access-date=5 September 2020}} {{PD-notice}}{{cite press release | publisher=Curium | title=RadioMedix and Curium Announce FDA Approval of Detectnet (copper Cu 64 dotatate injection) in the U.S. | via=GlobeNewswire | date=8 September 2020 | url=https://www.globenewswire.com/news-release/2020/09/08/2090352/0/en/RadioMedix-and-Curium-Announce-FDA-Approval-of-Detectnet-copper-Cu-64-dotatate-injection-in-the-U-S.html | access-date=9 September 2020}}
= Lutetium-177 DOTA-TATE =
{{main|Lutetium (177Lu) oxodotreotide}} {{see also|peptide receptor radionuclide therapy}}
The combination of the beta emitter 177Lu with DOTA-TATE can be used in the treatment of cancers expressing the relevant somatostatin receptors.{{cite journal | vauthors = Wang L, Tang K, Zhang Q, Li H, Wen Z, Zhang H, Zhang H | title = Somatostatin receptor-based molecular imaging and therapy for neuroendocrine tumors | journal = BioMed Research International | volume = 2013 | pages = 102819 | date = 2013 | pmid = 24106690 | pmc = 3784148 | doi = 10.1155/2013/102819 | doi-access = free}} The U.S. Food and Drug Administration (FDA) considers 177Lu-dotatate to be a first-in-class medication.{{cite report | title=New Drug Therapy Approvals 2018 | website=U.S. Food and Drug Administration (FDA) | date=January 2019 | url=https://www.fda.gov/media/120357/download | archive-url=https://web.archive.org/web/20190826114431/https://www.fda.gov/media/120357/download | url-status=dead | archive-date=26 August 2019 | format=PDF | access-date=16 September 2020}}
Alternatives to 177Lu-DOTA-TATE include 90Y (T1/2 = 64.6 h) DOTA-TATE. The longer penetration range in the target tissues of the more energetic beta particles emitted by 90Y (high average beta energy of 0.9336 MeV) could make it more suitable for large tumors while 177Lu would be preferred for smaller volume tumors.{{cite journal | vauthors = Ramage JK, Ahmed A, Ardill J, Bax N, Breen DJ, Caplin ME, Corrie P, Davar J, Davies AH, Lewington V, Meyer T, Newell-Price J, Poston G, Reed N, Rockall A, Steward W, Thakker RV, Toubanakis C, Valle J, Verbeke C, Grossman AB | display-authors = 6 | title = Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours (NETs) | journal = Gut | volume = 61 | issue = 1 | pages = 6–32 | date = January 2012 | pmid = 22052063 | pmc = 3280861 | doi = 10.1136/gutjnl-2011-300831}}{{cite journal | vauthors = Bodei L, Mueller-Brand J, Baum RP, Pavel ME, Hörsch D, O'Dorisio MS, O'Dorisio TM, O'Dorisiol TM, Howe JR, Cremonesi M, Kwekkeboom DJ, Zaknun JJ | title = The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours | journal = European Journal of Nuclear Medicine and Molecular Imaging | volume = 40 | issue = 5 | pages = 800–16 | date = May 2013 | pmid = 23389427 | pmc = 3622744 | doi = 10.1007/s00259-012-2330-6}}
See also
References
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